Abnormal brain inclusions chardc~ic of Abheimees disease (AD) are composed of paired helical filaments (PHn, a fibrillar form of tau (PBIF-tau). Various purification methods with and without proteolysis give filaments with different properties. We are attempting to obtain clean specimens and measure both helical parameters. and mass pe r unit length. Two different sucrose density-gradient fractions, of paired helical filaments (PIU) had different physical dimensions and masses. The size of the structural subunit ca n' be estimated for both fi-actions. Recent studies involve the structure of (paired helical) filaments grown in vitro with different isoforms of tau-protem. Masstlength measurements and radial mass profiles are being used to compare these filaments to in vtvo PBFs and to look at the role of phosphorylation of tau. Frequently, there is a very weird background on the carbon film. Different buffer systems are being explored. Eventually, the location of phosphorus in these filaments will be acandidate for STEM3 elemental mapping.